Estudio de equivalencia in vitro de algunos medicamentos de aciclovir, presentados como tabletas de liberación inmediata, comercializados en Colombia
ilustraciones
- Autores:
-
Sanchez Martinez, Angie Carolina
- Tipo de recurso:
- Fecha de publicación:
- 2023
- Institución:
- Universidad Nacional de Colombia
- Repositorio:
- Universidad Nacional de Colombia
- Idioma:
- spa
- OAI Identifier:
- oai:repositorio.unal.edu.co:unal/83120
- Palabra clave:
- 540 - Química y ciencias afines
Relación de equivalencia
Medicamentos genéricos
Equivalence relationship
Generic drugs
aciclovir
bioexención
bioequivalencia
disolución
acyclovir
biowaiver
bioequivalence
dissolution
- Rights
- openAccess
- License
- Atribución-NoComercial-SinDerivadas 4.0 Internacional
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Estudio de equivalencia in vitro de algunos medicamentos de aciclovir, presentados como tabletas de liberación inmediata, comercializados en Colombia |
| dc.title.translated.eng.fl_str_mv |
In vitro equivalence study of some aciclovir drugs, presented as immediate release tablets, marketed in Colombia |
| title |
Estudio de equivalencia in vitro de algunos medicamentos de aciclovir, presentados como tabletas de liberación inmediata, comercializados en Colombia |
| spellingShingle |
Estudio de equivalencia in vitro de algunos medicamentos de aciclovir, presentados como tabletas de liberación inmediata, comercializados en Colombia 540 - Química y ciencias afines Relación de equivalencia Medicamentos genéricos Equivalence relationship Generic drugs aciclovir bioexención bioequivalencia disolución acyclovir biowaiver bioequivalence dissolution |
| title_short |
Estudio de equivalencia in vitro de algunos medicamentos de aciclovir, presentados como tabletas de liberación inmediata, comercializados en Colombia |
| title_full |
Estudio de equivalencia in vitro de algunos medicamentos de aciclovir, presentados como tabletas de liberación inmediata, comercializados en Colombia |
| title_fullStr |
Estudio de equivalencia in vitro de algunos medicamentos de aciclovir, presentados como tabletas de liberación inmediata, comercializados en Colombia |
| title_full_unstemmed |
Estudio de equivalencia in vitro de algunos medicamentos de aciclovir, presentados como tabletas de liberación inmediata, comercializados en Colombia |
| title_sort |
Estudio de equivalencia in vitro de algunos medicamentos de aciclovir, presentados como tabletas de liberación inmediata, comercializados en Colombia |
| dc.creator.fl_str_mv |
Sanchez Martinez, Angie Carolina |
| dc.contributor.advisor.none.fl_str_mv |
Baena Ariztizábal, Yolima |
| dc.contributor.author.none.fl_str_mv |
Sanchez Martinez, Angie Carolina |
| dc.contributor.researchgroup.spa.fl_str_mv |
Sistema para Liberación Controlada de Moléculas Biológicamente Activas (SILICOMOBA) |
| dc.subject.ddc.spa.fl_str_mv |
540 - Química y ciencias afines |
| topic |
540 - Química y ciencias afines Relación de equivalencia Medicamentos genéricos Equivalence relationship Generic drugs aciclovir bioexención bioequivalencia disolución acyclovir biowaiver bioequivalence dissolution |
| dc.subject.lemb.spa.fl_str_mv |
Relación de equivalencia Medicamentos genéricos |
| dc.subject.lemb.eng.fl_str_mv |
Equivalence relationship Generic drugs |
| dc.subject.proposal.spa.fl_str_mv |
aciclovir bioexención bioequivalencia disolución |
| dc.subject.proposal.eng.fl_str_mv |
acyclovir biowaiver bioequivalence dissolution |
| description |
ilustraciones |
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2023 |
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2023-01-25T20:24:23Z |
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2023-01-25T20:24:23Z |
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2023-01-23 |
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Trabajo de grado - Maestría |
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info:eu-repo/semantics/masterThesis |
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Universidad Nacional de Colombia |
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Repositorio Institucional Universidad Nacional de Colombia |
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WHO. Expert Committee on Specificarions for Pharmaceutical Preparations. Fifty-first report. World Health Organization - Technical Report Series 2017:181. WHO Expert Committee on Specifications for Pharmaceutical Preparations. Annex 8 Guidance on the selection of comparator pharmaceutical. WHO Technical Report Series 2015: 185–9. Talevi A, Quiroga P, Ruiz E. Procesos biofarmacéuticos Su relación con el diseño de formas farmacéuticas y el éxito de la farmacoterapia. Editorial de la Universidad Nacional de la Plata; 2016. Ministerio de Salud y Protección Social. Resolución 1124 de 2016 "Por la cual se establece la Guia que contiene los criterios y requisitos para el estudio de Biodiponibilidad y Bioequivalencia de medicamentos, se define el listado de los que deben presentarlos y se establecen las condiciones de las instituciones que los realicen". 2016. Amidon GL, Lennernas H, Shah VP, Crison JR. A Theoretical Basis for a Biopharmaceutic Drug Classification: The Correlation of in Vitro Drug Product Dissolution and in Vivo Bioavailability. Pharm Res. 1995;12(3):413–20. U.S. Department of Health and Human Services. FDA Guidance for Industry. Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System. 2000. World Health Organization. Annex 8 Proposal to waive in vivo bioequivalence requirements for WHO Model List of Essential Medicines immediate-release , solid oral dosage forms. 2006: 391–437. Committee For Medicinal Products For Human Use. European Medicines Agency. Appendix III. BCS-Based Biowaiver. Guideline On The Investigation Of Bioequivalence. 2010: 710. Miranda-Pérez de Alejo C, Aceituno Álvarez A, Mendes Lima Santos G, Fernández Cervera M, Jung-Cook H, Cabrera-Pérez MÁ. Policy of Multisource Drug Products in Latin America: Opportunities and Challenges on the Application of Bioequivalence In Vitro Assays. Ther Innov Regul Sci [Internet]. 2021;55(1):65–81. Available from: https://doi.org/10.1007/s43441-020-00191-7 Miranda C, Aceituno A, Fernández M, Mendes G, Rodríguez Y, Llauró V, et al. ICH guideline for biopharmaceutics classification system-based biowaiver (M9): Toward harmonization in Latin American countries. Pharmaceutics. 2021;13(3). Organización Panamericana de la Salud. Guía para la implementación de estrategias de medicamentos genéricos en los países de America Latina y el Caribe como mecanismo para mejorar el acceso a medicamentos" (Documento No3 Serie Técnica de Medicamentos Esenciales, Polìticas Farnacéuticas). 2011: 1–45. Van der Plas H, Hardie D. Herpes simplex virus 1 and 2: A Therapeutic Approach. S Afr Pharm J. 2011;78(1):32–6. Susantakumar P, Gaur A, Sharma P. Feasibility biowaiver extension of immediate release oral acyclovir 800 mg tablet formulations : a BCS class III drug. Int J Pharm Pharm Sci. 2011;3(4):384–91. Arnal J, Bermejo M, Amidon GL, Junginger HE, Kopp S. Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms : Aciclovir. Wiley Intersci. 2008;97(12):5061–73. Mahmood A, Ahmad M, Sarfraz RM, Minhas MU, Yaqoob A. Development and In Vitro Evaluation of Acyclovir Rapid Dissolving Tablets : a Solubility and Bioavailability Enhancement Study. 2015;34(9):1701–9. OMS. Virus del herpes simple [Internet]. Datos cifras 2020. Available from: https://www.who.int/es/news-room/fact-sheets/detail/herpes-simplex-virus Zinser E, Krawczyk A, Mühl-zürbes P, Aufderhorst U, Draßner C, Stich L, et al. A new promising candidate to overcome drug resistant herpes simplex virus infections. Antiviral Res [Internet]. 2018;149(November 2017):202–10. Available from: https://doi.org/10.1016/j.antiviral.2017.11.012 García VM. Los medicamentos genéricos en Colombia: industria, políticas de salud y farmaceutización durante la década de 1960. Hist Crítica No40 [Internet]. 2017;65:115–37. Available from: https://appsciso.uniandes.edu.co/pfaciso/hcritica/view_s.php/14291/index.php?id=14291 M. Aranda, M.A. Rosasco, La farmacia de los medicamentos genéricos, Rev. Colomb. Cienc. Quím. Farm. 2019; 48(2): 357-371. Vaca C, Fitzgerald J, Bermúdez J. Definición de medicamento genérico ¿un fin o un medio? Análisis de la regulación en 14 países de la Región de las Américas. Rev Panam Salud Publica/Pan Am J Public Heal [Internet]. 2006;20(5):314–323. Available from: http://apps.who.int/medicinedocs/documents/s20131es/s20131es.pdf Who. How to develop and implement a national drug policy. WHO Policy Perspect Med [Internet]. 2003;6:1–6. Available from: http://archives.who.int/tbs/ndp/s4869e.pdf Aranda M, Rosasco MA. La farmacia de los medicamentos genéricos. Rev Colomb Ciencias Químico-Farmacéuticas. 2019;48(2):357–71. Delgado AB. Medicamentos genéricos, genéricos intercambiables, innovadores y el efecto terapéutico según la OMS y la legislación peruana. Crescendo Ciencias la Salud. 2016;3(1):183–9. Terán C, Jefe MT, Redacción D, Itsns D, Técnico C, Información U De. Medicamentos genéricos : una visión global. IT del Sist Nac Salud. 2010;34(2):35–40. Fagiolino P, Eiraldi R, Vázquez M. Intercambiabilidad de medicamentos. Bioequivalencia y equivalencia terapéutica. Acta Farm Bonaer. 2005;2(24):179–89. FDA. Guidance for Industry, Waiver of in vivo bioavailability and bioequivalence studies for immediate release solid oral dosage forms based on a biopharmaceutics classification system [Internet]. Center for Drug Evaluation and Research 2017:1–16. Available from: https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs Laosa O, Guerra P, Mosquera B, Frías J. Estudios De Bioequivalencia : La necesidad de establecer la fiabilidad de los medicamentos genéricos. Rev Peru Med Exp Salud Pública [Internet]. 2009;26(4):553–62. Available from: http://www.scielo.org.pe/pdf/rins/v26n4/a19v26n4 WHO Expert Committee on Specifications for Pharmaceutical Products. Annex 7 Multisource ( generic ) pharmaceutical products : guidelines on registration requirements to establish. 2006: 131–84. Moreno I. Optimización y mejora en la evaluación y análisis de los estudios de bioequivalencia [Tesis doctoral]. Madrid: Universidad Autonoma de Madrid; 2016. Recuperado partir de: https://repositorio.uam.es/bitstream/handle/10486/674495/moreno_arza_maria_isabel.pdf?sequence=1 FDA. Guidance for Industry Bioavailability and Bioequivalence Studies for Orally Administered Drug Productos - General Considerations. Estados Unidos; 2008. Ono A, Sugano K. Application of the BCS biowaiver approach to assessing bioequivalence of orally disintegrating tablets with immediate release formulations. Eur J Pharm Sci. 2014;64:37–43. Strauch S, Jantratid E, Dressman JB. Comparison of WHO and US FDA biowaver dissolution test conditions using bioequivalent doxycycline hyclate drug products. Pharm Pharmacol. 2010;61(3):331–7. FDA. U.S. Department of Health and Human Services. Guidance for Industry. Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on Biopharmaceutics Classification System. [Internet]. 2017: 2–19. Available from: https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs Administration, U.S. Department of Health and Human Services Food and Drug (CDER) C for DE and R. Dissolution Testing and Specification Criteria for Immediate-Release Solid Oral Dosage Forms Containing Biopharmaceutics Classification System Class 1 and 3 Drugs Guidance for Industry Dissolution Testing and Specification Criteria for Immediate-Release S. Food and Drug Administration Estados Unidos; 2015. FDA. Guidance for Industry Dissolution Testing of Immediate. Evaluation [Internet]. 1997;4:15–22. Available from: http://www.fda.gov/downloads/Drugs/.../Guidances/ucm070246.pdf Flanagan T. Potential for pharmaceutical excipients to impact absorption: A mechanistic review for BCS Class 1 and 3 drugs. Eur J Pharm Biopharm [Internet]. 2019;141:130–8. Available from: https://doi.org/10.1016/j.ejpb.2019.05.020 Parr A, Hidalgo IJ, Bode C, Brown W, Yazdanian M, Gonzalez MA, et al. The Effect of Excipients on the Permeability of BCS Class III Compounds and Implications for Biowaivers. Pharm Res [Internet]. 2016;167–76. Available from: http://dx.doi.org/10.1007/s11095-015-1773-4 Vaithianathan S, Haidar SH, Zhang X, Jiang W, Avon C, Dowling TC, et al. Effect of Common Excipients on the Oral Drug Absorption of Biopharmaceutics Classi fi cation System Class 3 Drugs Cimetidine and Acyclovir. J Pharm Sci [Internet]. 2016;105(2):996–1005. Available from: http://dx.doi.org/10.1002/jps.24643 Shah VP, Amidon GL. G.L. Amidon, H. Lennernas, V.P. Shah, and J.R. Crison. A Theoretical Basis for a Biopharmaceutic Drug Classification: The Correlation of In Vitro Drug Product Dissolution and In Vivo Bioavailability, Pharm Res 12, 413–420, 1995—Backstory of BCS. AAPS J [Internet]. 2014;16(5):894–8. Available from: http://link.springer.com/10.1208/s12248-014-9620-9 Dressman JB, Amidon GL, Reppas C, Shah VP. Dissolution Testing as a Prognostic Tool for Oral Drug Absorption: Immediate Release Dosage Forms. Pharm Res. 1998;15:11–22. Volont G, Quiroga P. Análisis farmacéutico. Primera ed. Universidad Nacional de La Plata – Editorial de la Universidad de La Plata, editor. Argentina; 2013. C. Pérez de Alejo. Propuesta de una metodología para el desarrollo de estudios de bioequivalencia in-vitro en la Unidad de Modelación y Experimentación Biofarmacéutica del Centro de Bioactivos Químicos [Tesis de pregrado]. Universidad Central “Marta Abreu” de Las Villas; 2016. Recuperado partir de: https://dspace.uclv.edu.cu/handle/123456789/7727 Saavedra I, Iturriaga V, Avila L, Quiñones L. Estudios de bioexención ( in vitro ) para establecer equivalencia de medicamentos Biowaiver studies ( in vitro ) to establish equivalence of drugs. Cuad Méd Soc [Internet]. 2011;52(2):66–79. Available from: http://www.captura.uchile.cl/bitstream/handle/2250/108236/Saavedra_et_al_2011-articulo.pdf?sequence=1 U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER). Dissolution Testing and Specification Criteria for Immediate-Release Solid Oral Dosage Forms Containing Biopharmaceutics Classification System Class 1 and 3 Drugs Guidance for Industry Dissolution Testing and Specification Criteria for Immediate-Release S. FDA Guidance for Industry Draft Guidance 2015: 5 U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER). Dissolution Testing and Acceptance Criteria for Immediate-Release Solid Oral Dosage Form Drug Products Containing High Solubility Drug Substances Guidance for Industry [Internet]. FDA Guidance for Industry Draft Guidance 2018 p. 5. Available from: http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm%0Afile:///C:/Users/ASUS/Desktop/Rujukan PhD/Drug Release/1074043 FNL_clean.pdf González I, Cabrera MÁ, Bemejo M. Metodologías Biofarmacéuticas en el desarrollo de medicamentos. Universidad Miguel Hernandez de Elche, Proyecto red Biofarma.; 2015: 1865. Leflore S, Anderson PL, Fletcher C V. A Risk-Benefit Evaluation of Aciclovir for the Treatment and Prophylaxis of Herpes Simplex Virus Infections. 2000;23(2):131–42. Nair AB, Attimarad M, Al-Dhubiab BE, Wadhwa J, Harsha S, Ahmed M. Enhanced oral bioavailability of acyclovir by inclusion complex using hydroxypropyl-β-cyclodextrin. Drug Deliv. 2014;21(7):540–7. USP. U.S. Pharmacopoeia-National Formulary 41 NF 36 (Vol. 41). In 2018. p. 84–5 Serra CH dos R, Storpirtis S. Comparação de perfis de dissolução da cefalexina através de estudos de cinética e eficiência de dissolução (ED%). Rev Bras Ciências Farm. 2007;43(1):79–88. Cárdenas P. Estudio de la correlación in vitro / in vivo de la liberación de 6 - metilcumarina a partir de un sistema micropartículado [Tesis doctoral].Bogotá D.C. Universidad Nacional de Colombia; 2016. Recuperado partir de: https://repositorio.unal.edu.co/bitstream/handle/unal/56673/cardenascuadrospaolaandrea.2015.pdf?sequence=1&isAllowed=y Simionato LD, Petrone L, Baldut M, Bonafede SL, Segall AI. Comparison between the dissolution profiles of nine meloxicam tablet brands commercially available in Buenos Aires, Argentina. Saudi Pharm J [Internet]. 2018;26(4):578–84. Available from: https://doi.org/10.1016/j.jsps.2018.01.015 Jung Cook H, de Anda Jáuregui G, Rubio Carrasco K, Mayet Cruz L. Comparación de perfiles de disolución. Impacto de los criterios de diferentes agencias regulatorias en el cálculo de f2. Rev Mex Ciencias Farm. 2012;43(3):67–71. Bhanu C. Bejgum, Johnson PR, William C. Stagner. Acyclovir chemical kinetics with the discovery and identification of newly reported degradants and degradation pathways involving for- maldehyde as a degradant and reactant intermediate. Int J Pharm. 2018; 535(1-2):172–179. Fonseca JC, Garzón López P. Efecto de la fuerza de compresión sobre los atributos críticos de calidad en tabletas de liberación inmediata de furosemida. Rev Colomb Ciencias Químico-Farmacéuticas [Internet]. 2017;46(2):235–55. Available from: https://revistas.unal.edu.co/index.php/rccquifa/article/view/67958 Shamshina JL, Cojocaru OA, Kelley SP, Bica K, Wallace SP, Gurau G, et al. Acyclovir as an Ionic Liquid Cation or Anion Can Improve Aqueous Solubility. ACS Omega. 2017;2(7):3483–93. Reddy NHS, Patnala S, Kanfer I. Investigation of Biowaivers for Immediate Release Formulations Containing BCS III Drugs, Acyclovir, Atenolol, and Ciprofloxacin Hydrochloride, Using Dissolution Testing. AAPS PharmSciTech [Internet]. 2017;18(2):424–31. Available from: http://dx.doi.org/10.1208/s12249-016-0520-4 Desai PM, Liew CV, Heng PWS. Review of Disintegrants and the Disintegration Phenomena. J Pharm Sci [Internet]. 2016;105(9):2545–55. Available from: http://dx.doi.org/10.1016/j.xphs.2015.12.019 |
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Atribución-NoComercial-SinDerivadas 4.0 Internacionalhttp://creativecommons.org/licenses/by-nd/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Baena Ariztizábal, Yolima227f7dbec7984e88472f8270735a5cbcSanchez Martinez, Angie Carolinacc6993a04763907ad678bea2116f7264Sistema para Liberación Controlada de Moléculas Biológicamente Activas (SILICOMOBA)2023-01-25T20:24:23Z2023-01-25T20:24:23Z2023-01-23https://repositorio.unal.edu.co/handle/unal/83120Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/ilustracionesEl presente estudio se realizó con el fin de determinar la posible equivalencia in vitro de dos medicamentos que contienen aciclovir en forma farmacéutica de tabletas de liberación inmediata frente al producto líder en el mercado en Colombia, de acuerdo con las directrices establecidas en la Resolución 1124 de 2016 del Ministerio de Salud y Protección Social. Para ello, se realizó la validación de la metodología analítica para la cuantificación del principio activo aciclovir, en cada uno de los niveles de pH evaluados, así como el control de calidad de los diferentes lotes de los tres productos que hacen parte del estudio, verificando el cumplimiento de las especificaciones establecidas en la monografía de aciclovir tabletas USP 41. Los perfiles de disolución en los tres niveles de pH (1,2; 4,5 y 6,8) se analizaron estadísticamente, comparando la eficiencia y el tiempo medio de disolución. Los resultados mostraron que, tanto el producto comparador como los dos productos de prueba se disolvieron muy rápidamente, por lo cual estos dos productos se consideraron equivalentes frente al líder del mercado y no fue necesaria la comparación de perfiles mediante el cálculo de los factores f1 y f2. De acuerdo con estos resultados, teniendo en cuenta que el aciclovir está clasificado como clase III en el sistema de clasificación biofarmacéutica, los productos evaluados se podrían considerar intercambiables desde la óptica de disolución, sin embargo, no se podría afirmar nada respecto a su equivalencia terapéutica debido a que el producto de referencia no se comercializa en el país. (Texto tomado de la fuente)The present study was carried out to determine the possible in vitro equivalence of two drugs products that contain acyclovir in tablets of immediate release against the lead market product in Colombia, according to the guidelines established in Resolution 1124 of 2016 from the Ministry of Health and Social Protection. For that reason, the validation of the quantification analytical methodology for the active pharmaceutical ingredient acyclovir was carried out in each one of the pH levels evaluated, so as the quality control of the different batches of the three products that conformed the study; the specifications were verified in accordance with the USP 41 monograph for acyclovir tablets. The three pH level dissolution profiles (1.2, 4,5 and 6,8) were statistically analyzed using the independent model method, comparing the efficiency and mean dissolution time. The results showed that both, the comparator product and the two tested products, dissolved very rapidly, therefore these two products were considered equivalent against the market leader and a profile comparison by calculating the f1 and f2 factor was not necessary. According to these results, considering that acyclovir is classified as class III in the biopharmaceutical classification system, the tested products could be considered interchangeable from the dissolution point of view, however, no affirmation could be done regarding its therapeutic equivalence because the reference product is not marketed in the country.MaestríaMagister en Ciencias Farmacéuticasxvii, 63 páginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Ciencias - Maestría en Ciencias FarmacéuticasFacultad de CienciasBogotá - ColombiaUniversidad Nacional de Colombia - Sede Bogotá540 - Química y ciencias afinesRelación de equivalenciaMedicamentos genéricosEquivalence relationshipGeneric drugsaciclovirbioexenciónbioequivalenciadisoluciónacyclovirbiowaiverbioequivalencedissolutionEstudio de equivalencia in vitro de algunos medicamentos de aciclovir, presentados como tabletas de liberación inmediata, comercializados en ColombiaIn vitro equivalence study of some aciclovir drugs, presented as immediate release tablets, marketed in ColombiaTrabajo de grado - Maestríainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionImageTexthttp://purl.org/redcol/resource_type/TMColombiaWHO. Expert Committee on Specificarions for Pharmaceutical Preparations. Fifty-first report. World Health Organization - Technical Report Series 2017:181.WHO Expert Committee on Specifications for Pharmaceutical Preparations. Annex 8 Guidance on the selection of comparator pharmaceutical. WHO Technical Report Series 2015: 185–9.Talevi A, Quiroga P, Ruiz E. Procesos biofarmacéuticos Su relación con el diseño de formas farmacéuticas y el éxito de la farmacoterapia. Editorial de la Universidad Nacional de la Plata; 2016.Ministerio de Salud y Protección Social. Resolución 1124 de 2016 "Por la cual se establece la Guia que contiene los criterios y requisitos para el estudio de Biodiponibilidad y Bioequivalencia de medicamentos, se define el listado de los que deben presentarlos y se establecen las condiciones de las instituciones que los realicen". 2016.Amidon GL, Lennernas H, Shah VP, Crison JR. 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Available from: http://dx.doi.org/10.1016/j.xphs.2015.12.019Estudio de equivalencia in vitro de algunos medicamentos de aciclovir, presentados como tabletas de liberación inmediata, comercializados en Colombia.Universidad Nacional de ColombiaPúblico generalORIGINAL1030538906.2022.pdf1030538906.2022.pdfTesis de Maestría en Ciencias Farmacéuticasapplication/pdf851675https://repositorio.unal.edu.co/bitstream/unal/83120/6/1030538906.2022.pdfed7a3dc4dde464aec8725b5d21e5c094MD56LICENSElicense.txtlicense.txttext/plain; charset=utf-85879https://repositorio.unal.edu.co/bitstream/unal/83120/7/license.txteb34b1cf90b7e1103fc9dfd26be24b4aMD57THUMBNAIL1030538906.2022.pdf.jpg1030538906.2022.pdf.jpgGenerated Thumbnailimage/jpeg5605https://repositorio.unal.edu.co/bitstream/unal/83120/8/1030538906.2022.pdf.jpg84970da7cc27a0a6f960ee992a81397bMD58unal/83120oai:repositorio.unal.edu.co:unal/831202023-08-13 23:05:44.121Repositorio Institucional Universidad Nacional de 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